New drug helps prostate cancer patients

Cristina Müller heads the Nuclide Chemistry research group at the Paul Scherrer Institute. Photo: Paul Scherrer Institute/Mahir Dzambegovic
Cristina Müller heads the Nuclide Chemistry research group at the Paul Scherrer Institute.

Researchers at the Paul Scherrer Institute (PSI) in Switzerland have developed a new drug that could increase the survival chances of patients with metastatic prostate cancer. 

The drug is now being tested on patients in the PROGNOSTICS project. A research consortium consisting of the PSI, the University Hospital Basel and ETH Zurich is receiving CHF 2 million ($2.2 million) in funding for this project. 

In Switzerland, about 7,100 men are diagnosed with prostate cancer every year. Around 1,400 of them die because the tumor has already metastasized and no longer responds to established treatments. Now there is new hope for these patients. 

In the PROGNOSTICS (PeRsOnalised theraGNOstics of metaStaTIC proState cancer) project, teams led by Roger Schibli of PSI, Damian Wild of the University Hospital Basel and Nicola Aceto of ETH Zurich are testing a new radioactive drug that may be more promising than existing radiopharmaceuticals. 

The study is scheduled to start in July 2023, the clinical trial starts in 2024 and will run until the end of 2025.

Hope for patients

About one third of patients with metastatic prostate cancer do not respond adequately to existing drugs: individual cancer cells can survive and form new metastases. In the future, new radionuclides could help such patients. The Paul Scherrer Institute has been carrying out research into a new isotope – terbium-161 – and its therapeutic uses for around 10 years now. In laboratory tests, Cristina Müller’s research group at PSI’s Centre for Radiopharmaceutical Sciences has demonstrated that the new terbium-161 can treat tumors effectively. In the context of PROGNOSTICS, the approach will be tested at the University Hospital Basel on 30 patients for whom other therapies have not had the desired success.

Drugs of this type – called radiopharmaceuticals – are radioactive substances injected into the bloodstream. The molecules are designed to attach themselves to the surface of tumor cells, like a key in a lock, but not to healthy cells. One end of the drug carries a radioactive atom that emits electrons (beta particles) during radioactive decay. These produce aggressive radicals inside the tumor cell, i.e. highly reactive substances that can attack the cell’s genetic material and thus destroy it.

The consortium has identified a possible reason why the radiopharmaceuticals currently used to treat prostate cancer do not work in a third of patients. The electrons emitted during radioactive decay deliver too small a dose to the smallest metastases or individual tumor cells, so that these are able to survive.

Destroying tumor cells with greater precision

In PROGNOSTICS, the partners are now testing a drug that uses the isotope terbium-161. This isotope emits electrons with a wide range of energies, including so-called conversion and Auger electrons. Due to their low energies, these have a range of just a few micrometers. They release all of their energy in a cell or in a cluster of cells, making their destructive power more precisely targeted. The tumor cell is damaged, is no longer able to divide and eventually dies, preventing the formation of metastases.

Preclinical studies in mice at PSI have already shown that this is a promising approach. In PROGNOSTICS, the new drug will now be tested at the University Hospital Basel.

The project is benefiting from the development of isotopes at PSI’s large research facilities, led by Nicholas van der Meulen. PROGNOSTICS brings together scientists from the fields of physics, chemistry, biology, pharmacology and medicine who are jointly developing the therapeutic approach from laboratory research to its application in patients. 

If PROGNOSTICS is successful and the anticipated goals are achieved, further, more extensive clinical trials are planned.

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